The Delaware Comprehensive Sickle Cell Research Program (a consortium between A.I. DuPont Hospital for Children and Delaware State Univ.) will build upon strengths in Biomedical Research, clinical care and recent recruitments to create a sustainable infrastructure supportive of target investigators and state-of-the art research. Three Target Investigator proposals and two Pilots comprise a well balanced research portfolio spanning basic science, translational and clinical aspects of Sickle Cell Disease (SCD). Target Project I deals with gene editing of the Q> Globin gene using TAL Effector Nucleases and single stranded oligonucleotides. Target Project II includes an evaluation of surrogate biomarkers of SCD-related pain in children and a Phase l/ll Trial of the n-3 Omega Fatty Acids in SCD-related pain and inflammation. Target Project III will use the Psychosocial Assessment Tool (PAT) to screen for risk in the pediatric population with SCD. The two Pilot Projects include studies on the in vitro growth of stem cells on nanofiber scaffolds, and the identification of genetic predictors of SCD-related stroke using next generation sequencing. The Overall Center Organization and Management Plan will incorporate key individuals, core facilities and resources previously funded through the IDeA Network, including the Center for Pediatric Research COBRE and the Delaware INBRE. A core will link advances in Health Informatics and electronic patient data recording with clinical research. Clinical data access and data integrity will provide a foundation for proposed and future clinical research. Strong Institutional support combined with federal dollars through the COBRE Program will ensure an outstanding program which will meet the ongoing needs of infants, children and adolescents with SCD and their families in Delaware. In addition, the research proposed will have a significant impact not only in the area of gene editing and in vitro stem cell growth but on SCD patient management in both the understanding and treatment of SCD related pain and stroke. The identification of the SCD affected family with high psychosocial risk will be also undertaken, facilitating appropriate evidence-based interventions that will diminish disparities in health care and outcomes.